The present proposal deals with reversible alterations of the BBB due to focal ionizing of radiation as a model for drug delivery to specific regions of the brain. This method has two advantageous features: 1) It expands the range of pharmacologically effective drugs to include those which cannot cross the intact BBB; 2) It can ensure that the drug crosses the BBB only in those regions which have been "opened" by radiation thus modifying the net effect of the drug. In the research already completed, we have shown that an experimentally produced focal epileptic lesion can be effectively controlled by intravenous gamma aminobutyric acid (GABA) only after the BBB has been previously opened by the focal radiation. To convert this method into one which might be clinically useful, the proposed research will follow three basic direction. (1) Methods to keep the BBB open: The most obvious way to keep the BBB open longer is with repeated radiation. Cats will be followed for reopening the BBB on recurrent radiation. Also, alumina gel induced epileptic foci will be reradiated to be followed with GABA suppression to see if the BBB remains open by this method. (2) Development of long-acting neuropharmacological agents: To achieve prolonged focal pharmacology, a variety of different drugs which can be delivered to the neurons while the BBB is open will be tested. Cats will be tested with a variety of amino acid anti-convulsants and general cytotoxic agents or specific neurotoxins. These latter drugs penetrating an opened BBB may be expected to kill the epileptic neurons and thus achieve a pharmocological "surgical excision". (3) Radio-Sterotatic localization of epileptic foci: We will use stereotactic radiation with GABA challenge to develop a diagnostic test for the stereotactic localization of epileptic foci. If an unsuppressible epileptic focus is indeed in the radiated area, then it will be come GABA suppressible and we will have confirmed the precise stereotatic coordinates of the focus.